The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers
Background Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TI...
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Korean Society of Pathologists & the Korean Society for Cytopathology
2025-01-01
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| Series: | Journal of Pathology and Translational Medicine |
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| Online Access: | http://www.jpatholtm.org/upload/pdf/jptm-2024-09-26.pdf |
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| author | Ji-Ae Lee Hye Eun Park Hye-Yeong Jin Lingyan Jin Seung Yeon Yoo Nam-Yun Cho Jeong Mo Bae Jung Ho Kim Gyeong Hoon Kang |
| author_facet | Ji-Ae Lee Hye Eun Park Hye-Yeong Jin Lingyan Jin Seung Yeon Yoo Nam-Yun Cho Jeong Mo Bae Jung Ho Kim Gyeong Hoon Kang |
| author_sort | Ji-Ae Lee |
| collection | DOAJ |
| description | Background Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Methods Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. Results CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]). Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC. |
| format | Article |
| id | doaj-art-48412f779ec2418486bf74b8d0fbf942 |
| institution | Kabale University |
| issn | 2383-7837 2383-7845 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Korean Society of Pathologists & the Korean Society for Cytopathology |
| record_format | Article |
| series | Journal of Pathology and Translational Medicine |
| spelling | doaj-art-48412f779ec2418486bf74b8d0fbf9422025-01-16T08:11:39ZengKorean Society of Pathologists & the Korean Society for CytopathologyJournal of Pathology and Translational Medicine2383-78372383-78452025-01-01591505910.4132/jptm.2024.09.2617129The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancersJi-Ae Lee0Hye Eun Park1Hye-Yeong Jin2Lingyan Jin3Seung Yeon Yoo4Nam-Yun Cho5Jeong Mo Bae6Jung Ho Kim7Gyeong Hoon Kang8 Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea Department of Pathology, Seoul National University Boramae Hospital, Seoul, Korea Department of Pathology, Seoul National University College of Medicine, Seoul, Korea Department of Pathology, Seoul National University College of Medicine, Seoul, Korea Pathology Center, Seegene Medical Foundation, Seoul, Korea Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea Department of Pathology, Seoul National University College of Medicine, Seoul, Korea Department of Pathology, Seoul National University College of Medicine, Seoul, Korea Department of Pathology, Seoul National University College of Medicine, Seoul, KoreaBackground Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Methods Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. Results CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]). Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.http://www.jpatholtm.org/upload/pdf/jptm-2024-09-26.pdfcd8 antigenscdx2 transcription factorcolorectal neoplasmsprognosislymphocytes, tumor-infiltrating |
| spellingShingle | Ji-Ae Lee Hye Eun Park Hye-Yeong Jin Lingyan Jin Seung Yeon Yoo Nam-Yun Cho Jeong Mo Bae Jung Ho Kim Gyeong Hoon Kang The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers Journal of Pathology and Translational Medicine cd8 antigens cdx2 transcription factor colorectal neoplasms prognosis lymphocytes, tumor-infiltrating |
| title | The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers |
| title_full | The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers |
| title_fullStr | The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers |
| title_full_unstemmed | The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers |
| title_short | The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers |
| title_sort | combination of cdx2 expression status and tumor infiltrating lymphocyte density as a prognostic factor in adjuvant folfox treated patients with stage iii colorectal cancers |
| topic | cd8 antigens cdx2 transcription factor colorectal neoplasms prognosis lymphocytes, tumor-infiltrating |
| url | http://www.jpatholtm.org/upload/pdf/jptm-2024-09-26.pdf |
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